Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B-lymphocyte precursors.

Uckun, Fatih M.; Schieven, Gary L.; Tuel‐Ahlgren, Lisa; Dıbırdık, İlker; Myers, Dorothea E.; Ledbetter, Jeffrey A.; Song, Chang W.

doi:10.1073/pnas.90.1.252

Cited by 118 publications

(46 citation statements)

References 24 publications

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“…However, the two TF-1 subclones exhibited similar PKC activity (data not shown). Alternatively, it is possible that, in TF-1-34 cells but not in TF-1-33 cells, IR could induce rapid PKC activation due to stimulation of phosphatidylinositol turnover (Uckun et al, 1993) or in relation with arachidonic acid production through phospholipase A 2 activation (Hallahan et al, 1994); sustained PKC stimulation could be, in turn, responsible for SMase inhibition. These hypotheses are currently being tested in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to ionizing radiation

et al. 1998

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The mechanism(s) by which ionizing radiation (IR) induces cell death is of fundamental importance in understanding cell sensitivity and resistance. Here we evaluated the response to IR of two subclones of the autonomous human erythromyeloblastic cell line TF-1: TF-1-34 (which expresses CD34) and TF-1-33 (which lacks CD34). In clonogenic assays, TF-1-34 cells were found to be relatively less sensitive to IR compared to TF-1-33 cells based on the D 0 determination (3.01 vs 1.56 Gy). Furthermore, after IR at 12 Gy, TF-1-33 cell viability decreased by *50% within 24 h, whereas TF-1-34 cell growth was unaffected during this time. Gradual loss of TF-1-34 cell viability was observed only after 48 h. Morphological and molecular analysis revealed that TF-1-33 cells died of apoptosis, and TF-1-34 cells of delayed reproductive cell death. While IR produced comparable amounts of DNA double strand breaks (DSB) in both cell lines, TF-1-34 retained DSB much longer than TF-1-33 suggesting that radioresistance and the defective apoptotic response of TF-1-34 cells was not related to a higher DNA repair capacity. However, the lack of an apoptotic response in TF-1-34 was correlated to the absence of a sphingomyelin (SM)-ceramide (CER) signaling pathway. Indeed, IR triggered in TF-1-33 cells but not in TF-1-34, SM hydrolysis (25% at 12 Gy) and CER generation (450%) through the activation of neutral but not acid sphingomyelinase. Synthetic cell permeate CER induced apoptosis in both TF-1-33 and TF-1-34 cells. This study indicates that alterations of the SM-CER signaling pathway can significantly influence the cell death process as well as the survival of acute myeloid leukemia cells after IR exposure.

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Section: Discussionmentioning

confidence: 99%

Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to ionizing radiation

et al. 1998

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“…For example, doxorubicin and cisplatin led to both rapid DAG accumulation and PKC stimulation (Posada et al, 1989;Rubin et al, 1992). IR has also been described to induce a rapid PKC activation due to stimulation of phosphatidylinositol turnover (Uckun et al, 1993). Overall, the observation that toxicants can modulate both CER and DAG levels has led to the speculation for the existence of a balance between pro-and antiapoptotic mediators, opposing the cytotoxic and the cytoprotective roles for CER and DAG, respectively (Kolesnick and Fuks, 1995).…”

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confidence: 99%

Daunorubicin- and Mitoxantrone-Triggered Phosphatidylcholine Hydrolysis: Implication in Drug-Induced Ceramide Generation and Apoptosis

et al. 1999

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Several studies have suggested that diacylglycerol can affect the induction of apoptosis induced by toxicants and ceramide. The present study demonstrates that clinically relevant concentrations of the chemotherapeutic drugs daunorubicin and mitoxantrone (0.2-1 M) transiently stimulated concurrently with sphingomyelin-derived ceramide generation and diacylglycerol and phosphorylcholine production within 4 to 10 min via phospholipase C hydrolysis of phosphatidylcholine. Pretreatment of cells with the xanthogenate compound D609, a potent inhibitor of phosphatidylcholine-phospholipase C, led to significant inhibition of drug triggered diacylglycerol and phosphorylcholine production and to a sustained increase in ceramide levels for a period up to 2 h. Moreover, D609 pretreatment induced both cell death and ceramide generation at daunorubicin and mitoxantrone concentrations previously shown to be ineffective (i.e., 0.1 M). These results underline the importance of diacylglycerol in the regulation of programmed cell death and strongly argue for a balance between apoptotic (ceramide) and survival (diacylglycerol) signal transducers.

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“…On the other hand, the ion assay appears to be impractical for routine use, because the number of ions released from cells by a given exposure are probably too small for reliable detection against the normal ionic concentrations of the cellular environment. Further development of cellular assays for light damage may productively utilize detection of various components of the "stress response" of mammalian cells (18), which is exhibited after exposure to various stressors including radiation (28), UV (9,26), oxidative stress (4,17), and activating agents such as phorbol esters (1,9). Because the stress response involves production of novel RNA messengers, proteins, or protein modifications, sensitive immunobiological and molecular probes may be used to detect the onset of cellular stress, and therefore provide the most accurate detection yet of threshold cellular changes after laser exposure.…”

Section: Discussionmentioning

confidence: 99%

“…Melanin, because of its broadband absorption characteristics, is efficient at converting photic to vibrational mode energy (22), and is certainly involved in tissue damage due to thermal and non-linear mechanisms (15,16,29). Now, there is increasing evidence that melanin, which forms a free radical when exposed to UV and visible wavelengths (8,21), may also be able to promote photochemical tissue damage (5,11,12,14,24,28). We initiated our investigations with the observation that during visible light exposure, RPE melanin rapidly oxidized ascorbic acid (vitamin C).…”

Section: Introductionmentioning

confidence: 99%

Investigation of Laser-Induced Retinal Damage: Wavelength and Pulsewidth Dependent Mechanisms

Glickman¹

1994

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Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B-lymphocyte precursors.

Cited by 118 publications

References 24 publications

Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to ionizing radiation

Lack of ceramide generation in TF-1 human myeloid leukemic cells resistant to ionizing radiation

Daunorubicin- and Mitoxantrone-Triggered Phosphatidylcholine Hydrolysis: Implication in Drug-Induced Ceramide Generation and Apoptosis

Investigation of Laser-Induced Retinal Damage: Wavelength and Pulsewidth Dependent Mechanisms

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